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PubMed2006

Noninvasive ratio indexes to evaluate fibrosis staging in chronic hepatitis C: role of platelet count/spleen diameter ratio index.

OBJECTIVES: Noninvasive evaluation of fibrosis is an on-going effort in the management of chronic hepatitis C. This study was planned to noninvasively evaluate fibrosis staging. DESIGN: We evaluated the biochemical, functional [aminopyrine breath test (ABT)] and ultrasonographic variables of 75 chronic hepatitis C patients. RESULTS: Clinical [body mass index (BMI)], biochemical [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT)] and ratio indexes, together with the ABT, showed a higher relationship with fibrosis: initial (score 2) fibrosis: BMI (24+/-2 vs. 26+/-2, P=0.0007), AST (56+/-36 vs. 88+/-65, P=0.0159), ALT (92+/-54 vs. 139+/-108, P=0.0290), PLT (220+/-64 vs. 173+/-61, P=0.0007), PLT/spleen diameter ratio (PLT/SPD) (2133+/-786 vs. 1540+/-681, P=0.0003), AST/platelet count ratio index (APRI) (0.80+/-0.87 vs. 1.51+/-1.47, P=0.0010), ABT%d/h30 min (10.8+/-4.5 vs. 7.6+/-3.8, P=0.0007), ABT%d/cum120 min (8.9+/-3.3 vs. 6.5+/-3.1, P=0.0007). Considering the differences between fibrosis score 2 and 3 patients, BMI, ABT and PLT/SPD ratio proved to be statistically significant. Multivariate stepwise analysis (with and without BMI) identified two models for distinguishing between initial and evident fibrosis: Model 1: -0.569+(BMIx0.107)+(APRIx0.169)-(PLT/SPDx0.304), and Model 2: 2.376+( APRIx0.152)-(ABTd/h30x0.043)-(PLT/SPDx0.249). These models showed concordance in identifying or ruling out evident fibrosis in 76% and 78.7% of the patients respectively. The PLT/SPD ratio also showed 78.7% concordance with the histological score. CONCLUSION: These results suggest that noninvasive evaluation of fibrosis in chronic hepatitis C may be considered an effective tool thanks to the use of an inexpensive, reproducible ratio index.

Adult↗
PubMed2003

L-[1-13C] phenylalanine breath test reflects histological changes in the liver.

OBJECTIVE: Compared with healthy individuals, patients with chronic liver disease reportedly have lower L-[1-13C] phenylalanine breath test (PBT) values. However, there is no report detailing the relationship between the results of PBT and pathological data in liver disease patients. This study was designed to investigate the degree of histological changes in the liver that induce PBT changes and the time of measurement that reflects the histological change. MATERIALS AND METHODS: PBT was performed in 47 patients (10 with a normal liver, and 37 with chronic hepatitis C). After administering 10 mg/kg L-[1-13C] phenylalanine, 300 mL of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (%13C dose h(-1)) at each time point was calculated from the amount of 13CO(2) in the exhaled air, assuming a CO(2) production rate of 300 mmol m(-2) body surface area per hour. Subsequently, we examined the relationship between the results of PBT and METAVIR pathological scoring. RESULTS: The highest correlation coefficients between the fibrosis score and %13C dose h(-1) and between the fibrosis score and %13C cumulative excretion were obtained at 45 min (r = -0.779, R(2) = 0.607; P < 0.0001) and 75 min (r = -0.768, R(2) = 0.590; P < 0.0001), respectively. CONCLUSION: PBT is a useful adjunct for detecting histological changes in the liver. The %13C dose h(-1) value at 45 min and the %13C cumulative excretion value at 75 min of PBT are useful for detecting hepatic histological change.

Biomarkers↗
PubMed2003

Lead exposure biomarkers and mini-mental status exam scores in older men.

BACKGROUND: Lead is neurotoxic; yet, whether cognitive decline in older persons is associated with lead exposure is unknown. We studied whether lead exposure biomarkers are associated with cognitive test scores, as well as the modifying effects of age on the lead-cognition relationship. METHODS: Lead exposure biomarkers and Mini-Mental Status Exam (MMSE) scores were measured among subjects in the Normative Aging Study. Multiple linear and logistic regression analyses were performed to examine the cross-sectional association of these 2 variables. RESULTS: We found an odds ratio (OR) of 2.1 for MMSE <24 with an increase from the lowest to the highest quartile of patella lead levels (95% confidence interval [CI] = 1.1 to 4.1). From the lowest to the highest quartile of blood lead the OR for low MMSE was 3.4 (CI = 1.6 to 6.2). There was an interaction between lead biomarkers and age. Among subjects in the lowest quartile of patella lead levels, MMSE score decreased by 0.03 points per year (CI = -0.07 to 0.005), whereas in the highest quartile, MMSE score decreased by 0.13 points per year (CI = -0.19 to -0.07). Similar interactions were found between blood lead levels and age. CONCLUSIONS: Increased levels of lead in bone and blood are inversely associated with cognitive performance among older men. Lead exposure might accelerate age-associated cognitive decline.

Aged↗
PubMed2006

CSF amyloid-beta-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia.

As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (Abeta) peptides, such as Abeta1-42. Absolute Abeta1-42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based Abeta-sodium-dodecylsulphate-polyacrylamide-gel-electrophoresis with Western immunoblot (Abeta-SDS-PAGE/immunoblot) revealed a highly conserved Abeta peptide pattern of the carboxy-terminally truncated Abeta peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42 in human CSF. We used the Abeta-SDS-PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the Abeta peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of Abeta peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases--Alzheimer's disease, DLB and PDD. The Abeta peptide patterns displayed disease-specific variations and the ratio of the differentially altered Abeta1-42 to the Abeta1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with Abeta-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized alpha-helical form of Abeta1-40 (Abeta1-40*). The increased abundance of Abeta1-40* probably reflects a disease-specific alteration of the Abeta1-40 metabolism in DLB. We conclude that Abeta peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although Abeta peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases.

Aged↗
PubMed2003

Mucin-depleted foci (MDF) in the colon of rats treated with azoxymethane (AOM) are useful biomarkers for colon carcinogenesis.

Crypt foci with absent or scant mucous production (mucin-depleted foci, MDF) were recently described by our group in the colon of azoxymethane (AOM)-treated rats. Since MDF are dysplastic and easy to quantify, we think that MDF are pre-neoplastic lesions that could be used as biomarkers for carcinogenesis. To test this hypothesis, we studied MDF in azoxymethane (AOM)-initiated rats treated with cholic acid (CHA), a promoter of colon carcinogenesis or with piroxicam (PXC), a colon cancer-inhibiting drug. Aberrant crypt foci (ACF) were determined as well. F344 male rats were treated with AOM (15 mg/kg x 2, s.c.) and then divided into: controls, which were fed AIN76 diet; CHA group, which was fed AIN76 diet containing CHA 0.5% w/w; PXC group, which was fed AIN76 diet containing PXC 0.02% w/w. Ten weeks after the first dose of AOM, the total number of MDF was significantly increased in rats treated with CHA (P<0.05) and drastically reduced (P<0.01) in rats treated with PXC (MDF/colon were 6.10 +/- 1.26, 10.59 +/- 1.96 and 1.31 +/- 0.21 in controls, CHA and PXC groups, respectively, means +/- SE). The multiplicity of MDF was also increased in CHA-treated rats. On the contrary, ACF multiplicity was significantly decreased by CHA. In PXC-treated rats there were fewer ACF with lower multiplicity. The effect of PXC was also investigated 15 weeks after the first AOM dose and the results showed that the total number of MDF in the PXC group was significantly lower than in controls. The number of 'large' MDF, formed by 12 or more crypts, was also reduced (P<0.01) by PXC ('large' MDF were 1.7 +/- 0.5 and 0.4 +/- 0.2 in control and PXC groups, respectively). Since CHA promotes and PXC reduces colon cancer, MDF are correlated with carcinogenesis and can be proposed as endpoints to study the modulation of colon carcinogenesis in short-term experiments.

Animals↗
PubMed2003

Chylomicron remnant metabolism studied with a new breath test in postmenopausal women with and without type 2 diabetes mellitus.

OBJECTIVES: The kinetic basis for the effect of type 2 diabetes mellitus (DM) on postprandial lipoproteins has not been fully established. We investigated chylomicron remnant metabolism using a stable isotope breath test and fasting measurements of plasma apolipoprotein (apo) B-48 and apoC-III concentrations in postmenopausal women with and without type 2 DM. PATIENTS: Twenty-four postmenopausal women without DM and 14 postmenopausal women with diet-controlled DM of similar age and body mass index (BMI) were studied in the postabsorptive state. METHODS: The fractional catabolic rate (FCR) of an intravenously injected chylomicron remnant-like emulsion was determined from the appearance of 13CO2 in the breath using isotope-ratio mass spectrometry and multicompartmental modelling. apoB-48, a marker of particle number of intestinal lipoproteins, was determined immunoelectrophoretically. apoC-III was measured by immunoturbidimetric assay. RESULTS: Compared with the nondiabetic women, the women with DM had significantly higher plasma apoB-48 concentration (16.40 +/- 1.18 mg/l vs. 13.0 +/- 0.9 mg/l; mean +/- standard error mean; P = 0.021), higher plasma apoC-III concentration (204.24 +/- 15.18 mg/l vs. 170.74 +/- 10.75 mg/l; P = 0.042) and lower FCR of the chylomicron remnant-like emulsion (0.06 +/- 0.05 pools/h vs. 0.12 +/- 0.02 pools/h; P < 0.001). In the diabetic patients, the FCR of the emulsion was correlated significantly with plasma apoB-48 levels (r = -0.641, P = 0.007) but not with apoC-III levels. CONCLUSIONS: In postmenopausal women, diabetes mellitus appears to decrease the catabolism of chylomicron remnants and result in an accumulation of these particles in plasma. This may chiefly be due to decreased clearance by hepatic receptors related to an effect of insulin resistance. Impairment in the catabolism of chylomicron remnants may contribute to increased risk of atherosclerosis in postmenopausal women with type 2 diabetes mellitus.

Apolipoprotein B-48↗
PubMed2005

Use of exhaled nitric oxide measurements to guide treatment in chronic asthma.

BACKGROUND: International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FE(NO)) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment. METHODS: In a single-blind, placebo-controlled trial, we randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FE(NO) measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid. RESULTS: Forty-six patients in the FE(NO) group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 microg per day for the FE(NO) group (95 percent confidence interval, 263 to 477) and 641 microg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 microg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FE(NO) group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a nonsignificant reduction of 45.6 percent (95 percent confidence interval for mean difference, -78.6 percent to 54.5 percent) in the FE(NO) group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils). CONCLUSIONS: With the use of FE(NO) measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Administration, Inhalation↗
PubMed1997

Quantitative liver function tests as surrogate markers for end-points in controlled clinical trials: a retrospective feasibility study.

Quantitative liver function tests such as the determination of galactose elimination capacity (GEC) or the aminopyrine breath test (ABT) may have the potential to serve as refined entry criteria and surrogate markers for end-points in controlled clinical trials. The magnitude of a statistically detectable difference in test results and the period of observation required to document such a difference must be known to properly design such trials. Therefore, we explored retrospectively the time course of changes in GEC and ABT and their reproducibility from a cohort of patients with alcoholic cirrhosis followed for 12 to 42 months, with a median of 34 months. In 15 patients who stopped drinking, GEC improved significantly by 0.64 mg/min/kg within 1 year (mean; 95% confidence interval [CI]: 0.42; 0.86). In contrast, it deteriorated by 0.53 mg/min/kg within 1 year (95% CI: 0.32; 0.74) in another 17 patients who continued to drink (P < .01). The residual standard deviation of the changes in GEC with respect to the patients' initial values was 0.43 mg/min/kg (95% CI: 0.32; 0.52). In addition, ABT improved significantly by 0.14% dose x kg/mmol CO2 (95% CI: 0.09; 0.18) in the abstinent group, and deteriorated by 0.09% dose x kg/mmol CO2 (95% CI: 0.06; 0.13) in the nonabstinent group (P < .01). The residual standard deviation in the above sense for ABT was 0.08% dose x kg/mmol CO2 (95% CI: 0.06; 0.10). These data indicate that clinical trials with a sample size of n = 20 in each group must achieve absolute differences (ADs) in GEC of 0.6 mg/min/kg and of 0.7 mg/min/kg to reach statistical significance at the 5% and 1% level, respectively. In the present study, a period of 11 and 12 months was necessary to observe such differences. The corresponding results for the ABT are 0.11% dose x kg/mmol CO2 (9 months of follow-up; 5% level) and 0.13% dose x kg/mmol CO2 (11 months of observation; 1% level), respectively. Provided that patients with liver diseases treated with drugs are similar to the abstinent and nonabstinent patients with alcoholic liver disease investigated in this study, such numbers could serve for the planning of controlled clinical trials, in which the control group is likely to deteriorate and the treated group is expected to improve. Trials based on GEC or ABT would require only 37 or 30 patient years of observation compared with a median of 444 patient years (range, 50-2,100 patient years) reported for various published controlled clinical trials using survival analysis.

Adult↗
PubMed2006

Robust analysis of biomarker data with informative missingness using a two-stage hypothesis test in an HIV treatment interruption trial: AIEDRP AIN503/ACTG A5217.

Clinical trial AIN503/A5217 investigates whether a period of early treatment with antiretroviral therapy might lower the viral setpoint in subjects recently infected with HIV-1. We consider two statistical issues. First, even under the null hypothesis control arm subjects are more likely than treatment arm subjects to be missing final outcome data because of disease progression. The analysis must adjust for this missing data, or it may be unacceptably biased. Second, comparing outcomes between treatment and control arms at identical times post-randomization gives different information than comparing outcomes at the same amount of time off-therapy, as measured post-randomization. This may make interpretation of results problematic. We formulate the null hypothesis of the study as exchangeability under a time-shift between arms, which we call "time delay" between the study arms. This captures clinically relevant information, and allows us to formalize a two-stage hypothesis test in which stage one is a comparison between arms at identical times post-randomization, and stage two is a comparison between arms at identical times off-therapy, as measured post-randomization. Importantly, within this framework we can show that the two-stage test can be adjusted for the missing data using a simple worst-rank substitution.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Detection of isoprene in expired air from human subjects using proton-transfer-reaction mass spectrometry.

A new analytical method using proton-transfer-reaction mass spectrometry (PTRMS) is described for the determination of trace constituents in human breath. PTRMS is sufficiently sensitive and specific that it does not require preconcentration or separation. At its present stage of development it is capable of detecting trace constituents present in air at the part-per-billion level. These capabilities are illustrated for isoprene, one of the most abundant endogenous hydrocarbons. Our results confirm recent observations of a diurnal level variation associated with sleep or wakefulness; a new finding is that young children have much lower levels of isoprene in breath than adults. To address the metabolic origin of human isoprene, we used PTRMS to analyze expired air for allylic C5 alcohols that have been proposed to be non-enzymatic precursors of isoprene. The lack of correlation between peak breath isoprene and these alcohols suggests that the hydrocarbon is formed by some other mechanism.

Adult↗
PubMed1997

Decreased concentration of exhaled nitric oxide (NO) in patients with cystic fibrosis.

Nitric oxide (NO) is produced by various cell types in the human respiratory tract. Endogenously produced nitric oxide is detectable in the exhaled air of healthy individuals. Exhaled NO has been shown to be increased in airway inflammation, most probably due to cytokine-mediated activation of NO synthases. To assess whether NO can serve as a marker of inflammation in cystic fibrosis (CF) lung disease, we measured exhaled NO in CF patients with a chemiluminescence analyser. Single breath measurements were performed in 27 stable CF patients (age range, 6-40 years) and 30 non-smoking controls (age range, 6-37 years). Exhaled NO concentrations were 9.1 +/- 3.6 ppb in the controls and 5.9 +/- 2.6 ppb (P < 0.001) in CF patients. To account for room air NO concentrations on the measurement of exhaled NO, we also calculated the difference between exhaled NO and ambient NO concentrations. Difference values were also significantly lower in CF compared with controls (P < 0.0001). In CF patients there was a positive correlation between exhaled NO and forced vital capacity (r = 0.43, P = 0.033), suggesting that exhaled NO is lower in patients with severe lung disease than in those with mild disease. We conclude that measurements of exhaled NO in CF does not reflect activity of CF airway inflammation. The decreased concentrations of exhaled NO may be due to inhibitory effects of inflammatory cytokines on NO syntheses in the airways and alveolar epithelial cells or to increased retention in airway secretions.

Adolescent↗
PubMed1999

Non-invasive biomarkers of asthma.

Several non-invasive biomarkers of inflammation in asthma such as exhaled NO and eosinophil numbers in induced sputum have been developed. Their usefulness in experimental asthma models has been validated but there is less experience in their use in clinical practice. Because specific cooperation may be needed from the patient in producing samples from the airways for assay of biomarkers, younger children may not be suitable. Specific experience in these age groups is required. There remains a need to examine these biomarkers in patients from the mild asymptomatic to the more symptomatic difficult asthmatic in longitudinal studies. Is it useful to monitor these biomarkers as a response to treatment rather than the more conventional measures of symptoms and lung function measurements for prevention of exacerbations and long-term reduction in lung function? Answers to such issues will be crucial in adopting the routine measurement of certain biomarkers from the airways in the assessment of asthma severity and control.

Asthma↗
PubMed1999

Exhaled nitric oxide before and after montelukast sodium therapy in school-age children with chronic asthma: a preliminary study.

Exhaled nitric oxide (ENO) is a surrogate marker of airway inflammation in asthma. In 12 children aged 6-11 years with mild to moderate persistent asthma, ENO concentrations were measured before and after 4 weeks of treatment with montelukast sodium, a leukotriene receptor antagonist, and 2 weeks after withdrawal of therapy. Baseline ENO levels (mean and 95% confidence interval) were significantly elevated in patients with asthma compared to age-matched nonasthmatic control subjects, with levels of 83 (42-123) vs. 13 (11-15) ppb (P < 0.001). After treatment with montelukast sodium, there was a significant (P < 0.01) reduction in ENO to 58 (27-89) ppb which again rose to 69 (38-99) ppb 2 weeks after treatment was withdrawn. During treatment, the fall in ENO was accompanied by nonsignificant improvements in prebronchodilator forced expiratory volume in 1 s (FEV(1)) from 81-85% predicted or reductions in use of albuterol from a mean of 2.5 to 1.6 puffs/day. Individual ENO measurements and change in ENO concentrations with treatment did not correlate with either pulmonary function changes or use of bronchodilator. These data show that ENO is elevated in children with relatively mild asthma treated with bronchodilator alone, and that treatment with montelukast sodium for 4 weeks results in a significant reduction in ENO concentrations, even in the absence of significant changes in pulmonary function. These findings suggest an anti-inflammatory role for leukotriene D(4) receptor antagonism in the treatment of children with mild to moderate asthma.

Acetates↗
PubMed2004

Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood cell survival.

A major side effect of ribavirin (RBV) treatment is anemia. While this anemia is thought to result from increased RBC turnover, RBC survival has not been determined in subjects receiving RBV due to the complexity of the techniques commonly used to quantitate RBC life span. We recently described a simple, rapid, non-invasive technique that utilizes measurements of alveolar carbon monoxide (CO) concentration to determine RBC survival. In the present report, this method was employed to assess RBC survival in patients receiving RBV for hepatitis C. Each of the 31 measurements of RBC survival in 12 subjects with RBV-associated anemia was below the lower limit of normal (77 days), and the average survival (46 +/- 14 days) in these subjects was only about 38% of that of healthy controls (122 +/- 23 days). Five hepatitis C patients not undergoing RBV treatment had normal RBC survivals (112 +/- 17 days). While the mean reticulocyte percentage was significantly elevated in subjects treated with RBV, 59% of these measurements fell within the limits of normal. We conclude that RBV-associated anemia consistently is associated with reduced RBC survival as determined from breath CO measurements and that this reduced survival frequently is not associated with an elevated reticulocyte count.

Adult↗
PubMed2003

Association of expired nitric oxide with urinary metal concentrations in boilermakers exposed to residual oil fly ash.

BACKGROUND: Exposure to metal-containing particulate matter has been associated with adverse pulmonary responses. Metals in particulate matter are soluble, hence are readily recovered in urine of exposed individuals. This study investigated the association between urinary metal concentrations and the fractional concentration of expired nitric oxide (F(E)NO) in boilermakers (N = 32) exposed to residual oil fly ash (ROFA). METHODS: Subjects were monitored at a boiler overhaul site located in the New England area, USA. F(E)NO and urine samples were collected pre- and post-workshift for 5 consecutive workdays. Metals investigated included vanadium (V), chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), and lead (Pb). RESULTS: The median F(E)NO was 7.5 ppb (95% CI: 7.4-8.0), and the median creatinine-adjusted urinary metal concentrations (mug/g creatinine) were: vanadium, 1.37; chromium, 0.48; manganese, 0.30; nickel, 1.52; copper, 3.70; and lead, 2.32. Linear mixed-effects models indicated significant inverse exposure-response relationships between log F(E)NO and the log-transformed urinary concentrations of vanadium, manganese, nickel, copper, and lead at several lag times, after adjusting for smoking status. CONCLUSIONS: Urine samples may be utilized as a biomarker of occupational metal exposure. The inverse association between F(E)NO and urinary metal concentrations suggests that exposure to metals in particulate matter may have an adverse effect on respiratory health.

Adolescent↗
PubMedDate not supplied

Thermal desorption-gas chromatographic determination of ethane and pentane in breath as potential markers of lipid peroxidation.

Formation of free radicals and lipoperoxidation occur at the onset of cellular damage. These effects are produced during normal metabolism and in pathological states. The peroxidation of polyunsaturated fatty acids, i.e. linoleic acid and linolenic acid, which are both cellular membrane compounds, induces ethane and pentane formation in pulmonary air exhalation. These two volatile hydrocarbons can be considered as potential lipoperoxidation markers. Methodological difficulties limit the use of these gases for assessment of free oxygen radical activity but we have developed and validated a non-invasive technique. A study was performed with ten healthy volunteers.

Biomarkers↗
PubMed2006

HPV-mediated cervical carcinogenesis: concepts and clinical implications.

Persistent infection with a high-risk human papillomavirus (hrHPV) is generally accepted as a necessary cause of cervical cancer. However, cervical cancer is a rare complication of an hrHPV infection since most such infections are transient, not even giving rise to cervical lesions. On average, it takes 12-15 years before a persistent hrHPV infection may ultimately, via consecutive premalignant stages (ie CIN lesions), lead to an overt cervical carcinoma. This argues that HPV-induced cervical carcinogenesis is multi-step in nature. In this review, the data from hrHPV-mediated in vitro transformation studies and those obtained from analysis of clinical specimens have been merged into a cervical cancer progression model. According to this model, a crucial decision maker in the early stages following infection involves individual susceptibility for certain HPV types depending on the genetic make-up of immune surveillance determinants. Once a CIN lesion has developed, altered transcriptional regulation of the viral E6/E7 oncogenes, resulting in genomic instability and distinguishing the process of cell transformation from a productive viral infection, probably provides the subsequent important step towards malignancy. The additional (epi)genetic alterations that subsequently accumulate in high-grade CIN lesions may result in overt malignancy via immortality and growth conditions that gradually become less sensitive to growth-modulating influences mediated by cytokines and cell-cell and cell-matrix adhesions. The potential implications of hrHPV testing and some other biomarkers deduced from this model for cervical screening and the clinical management of CIN disease are also discussed.

Cell Adhesion Molecule-1↗